The use of extracts obtained from Chenopodium ambrosioides for controlling established insect or mite infestations on plants has been described previously, including the use of such extracts that include natural terpenes isolated from Chenopodium. See, for example, US Published Patent Application Nos. 2003/0091657 and 2009/0030087; PCT Publication Nos. WO 2001/067868 and WO 2004/006679; William Quarles (1992) Botanical Pesticides from Chenopodium, The IPM Practitioner Volume XIV, Number 2, 11 pages; and Lorenzo Sagrero-Nieves (March/April 1995) Volatile Constituents from the Leaves of Chenopodium ambrosioides L., J. Essent. Oil Res. 7:221-223, each of which is specifically incorporated by reference herein in its entirety. The prior art teaches that such extracts can be applied to plants to kill or otherwise control certain insect species and/or mites on plants.
The prior art, however, does not appreciate that simulated blends comprising substantially pure terpenes can effectively mimic the insecticidal and acaricidal activity of the Chenopodium plant extracts. There is a long-standing need to substitute natural extract from plants with active substantially pure chemicals which can mimic the functions of the natural extract when mixed, due to limited availability of plant resources, variability in plant extract compositions, longer production cycle and higher cost of natural extract compared to synthetic chemicals. However, it has been always a challenge for researchers to identify the active ingredients in the natural extracts from plants, and even if such ingredients were identified, problems still remain: in some cases, such ingredients can not be synthesized through known pathways; in other cases, even if such ingredients could be synthesized, a mere combination of them may recapitulate no, or much lower, activity compared to the natural extract.
For example, despite the fact that Marinol (dronabinol) is the only US FDA-approved synthetic cannabinoid (chemical compound in natural cannabis), it typically provides only limited relief to select patients, particularly when compared to natural cannabis and its cannabinoids, since several other cannabinoids in cannabis may also contribute to the therapeutical effect, and synergism exists when these compounds are applied together.
For another example, it has been more and more accepted that synthetic crystalline vitamins differ from vitamins in natural products in many ways, since vitamins in natural products are complexes of critical combinations and cannot be split off without destroying the biological activities, while synthetic vitamins are only synthesized fractions of a vitamin complex.
For yet another example, in Jiang, Z., et al., “Comparative Toxicity of Essential Oils of Litsea pungens and Litsea cubeba and Blends of Their Major Constituents against the Cabbage Looper, Trichoplusia ni” J. Agric. Food Chem. (2009) 57, 4833-4837, the authors describe the extract of L. cubeba, which includes the major terpenes present in Chenopodium, α-terpinene, d-limonene and p-cymene, as well as other components. The Jiang reference notes that mortality caused by mixtures of the six known components of the extract was significantly lower than that caused by the natural essential oil, suggesting that the 10% of the unknown constituents had a significant contribution to toxicity. Further, a combination of γ-terpinene, R-limonene and p-cymene was only 40% effective against Trichoplusia ni and a combination containing α-terpinene, β-pinene and α-pinene had almost no mortality against T. ni larvae.
Beghyn et al., Natural Compounds: Leads or Ideas? Bioinspired Molecules for Drug Discovery, 28 Jun. 2008, Chemical Biology & Drug Design, 72(1):3-15, summarize the results of their review as follows: “In this article, we compare drugs of natural origin to synthetic compounds and analyze the reasons why natural compounds occupy a place of choice in the current pharmacopoeia.” Thus, it is well known by those skilled in the art that the synthetic analog of a natural extract may have very different biological activities. This is particularly so where, as in the present invention, the extract contains more than one active ingredient.
U.S. Patent Application Publication Nos. 2008/0075796 and 2008/0020078 describe some synergistic combinations of plant oils for controlling insects. These publications provide long lists of essential oils, including selected terpenes, that may or may not be included in such compositions. These publications fail to provide specific guidance or examples that would lead one of ordinary skill in the art to arrive at the simulated, synthetic terpene compositions of the present invention or to use the simulated, synthetic terpene compositions of the present invention to control insects. For example, US Patent Application Publication No. 2008/0075796 describes a composition comprising d-limonene, α-pinene and p-cymene that is shown as being active against only farm ants. As demonstrated by the Jiang reference described above, it is not possible to simply combine various terpenes without testing specific combinations and amounts of such terpenes to arrive at insecticidally effective compositions.
Thus, the simulated, synthetic and synergistic pesticidal compositions of the present invention are not obvious over the prior art, since a person with ordinary skill in the art will not be able to predict the necessary active ingredients to be combined to make such pesticidal compositions and the synergistic pesticidal effects of the compositions.
In addition, the prior art does not appreciate that certain terpene extracts obtained from Chenopodium ambrosioides, natural analogs of such terpenes from other plant species or other organisms, and/or the synthetic versions of such terpenes can also be used in preventative or prophylactic methods of plant protection (i.e., applied to plants before the insects and/or mites reach the economic threshold on the plants). Furthermore, the prior art does not appreciate that such terpene extracts, natural analogs of such terpenes from other plant species or other organisms, and/or synthetic versions of such extracts, can be used to kill or otherwise control lepidopteran plant pests.
Furthermore, the prior art does not appreciate that such terpene extracts, natural analogs of such terpenes from other plant species or other organisms, and/or synthetic versions of such extracts, can be used to kill or otherwise control lepidopteran plant pests. While Highland et al. (Submitted Paper Abstracts, Entomological Society of America Eastern Branch 78th Annual Meeting, March 2007, Appendix F, page 55) provide some information showing that extracts obtained from Chenopodium ambrosioides can control sod webworms (when applied at rates that are at least 300 times the norm for the extracts) and spotted tentiform leafminers, it remained unappreciated until the present invention that such terpenes can control a wider variety of lepidopteran species when applied at lower rates under both field and greenhouse conditions.